Protective Effect of Nicotine on Sepsis-Induced Oxidative Multiorgan Damage: Role of Neutrophils

Kumral, Zarife Nigar Özdemir; Özbeyli, Dilek; Özdemir, Ahmet Faruk; Karaaslan, M. Buğra; Kaytaz, Kübra; Kara, Mustafa; Tok, Olgu Enis; Ercan, Feríha; Yeğen, Berrak Ç.

doi:10.1093/ntr/ntw198

Cited by 15 publications

(15 citation statements)

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“… 20 Activation of CAIP by long-term nicotine administration reduces sepsis-induced oxidative damage in several tissues including liver which appears to involve inhibition of neutrophil activity in the inflamed tissues. 21 Likewise, high frequency VNS improves portal hypertension in cirrhotic rats. 22 Clinical evidence indicates that when vagus nerve activity is deficient, inflammation is excessive.…”

Section: Introductionmentioning

confidence: 97%

Cholinergic Anti-Inflammatory Pathway and the Liver

Hajiasgharzadeh¹,

Baradaran²

2017

Adv Pharm Bull

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The hepatic vagus branches innervate the liver and serve an important role in liver-brain connection. It appears that brain modulates inflammatory responses by activation of vagal efferent fibers. This activation and subsequent acetylcholine releases from vagus nerve terminals leads to inhibition of inflammatory cytokines through α7 nicotinic acetylcholine receptors (α7nAChRs) which located on the surface of different cell types such as liver Kupffer cells. This protective role of vagus-α7nAChR axis in liver diseases has been shown in several experimental studies. On the other hand, accumulated evidence clearly demonstrate that, autonomic dysfunction which is reduced functioning of both vagal and sympathetic nervous system, occurs during chronic liver disease and is well-known complication of patients suffering from cirrhosis. This review describes the impact and significance of cholinergic anti-inflammatory pathway in the liver and discusses about its disease-related dysfunction on the progression of cirrhosis. Considering the fact that sepsis is major cause of death in cirrhotic patients, convergence of these findings, may lead to designing novel therapeutic strategies in the field of chronic liver diseases management involving selective drug targeting and electrical nerve stimulation.

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Section: Introductionmentioning

confidence: 97%

Cholinergic Anti-Inflammatory Pathway and the Liver

Hajiasgharzadeh¹,

Baradaran²

2017

Adv Pharm Bull

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“…Buna karşın, MDA, MPO ve GSH düzeylerindeki nikotin tedavisiyle ilişkili iyileşmelerin vagal denervasyondan etkilenmemesi nikotinin direkt antioksidan etkisini düşündürmektedir. Benzer şekilde, sepsise bağlı gelişen çoklu organ hasarında da nikotinin akciğer dokusu haricinde lipit peroksidasyonunu sınırlayarak, GSH tüketimini engelleyerek ve MPO aktivitesini baskılayarak anti-inflamatuvar etkili olduğu gösterilmiştir (21).…”

Section: Discussionunclassified

“…Bu hastalıklarda, örneğin osteoartritte (16) veya ülseratif kolitte (17,18), nikotin hastalığın gelişmesini geciktirmekte veya antioksidan etkisiyle inflamasyon şiddetini azaltmaktadır. Benzer şekilde, nikotin inflamasyon indüklenmiş çeşitli dokularda hastalık şiddetini azaltmakta ve iyileşme sürecini hızlandırabilmektedir (19)(20)(21).…”

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Investigation of The Role of Vagus in The Ameliorative Effect of Nicotine on Rat Pancreatitis Model

Kolgazi¹,

Güleken²,

Kolbaşı³

et al. 2021

Acibadem Universitesi Saglik Bilimleri Dergisi

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Nikotinin birçok farklı dokuda anti-inflamatuvar etkilere sahip olduğu ve bu etkileri kolinerjik anti-inflamatuvar yolağı aktive ederek gerçekleştirdiği gösterilmiştir. Çalışmada akut pankreatit modelinde nikotin tedavisinin etkilerini ve bu etkilerin kolinerjik yolla ilişkisini araştırmak amaçlanmıştır. Wistar albino sıçanların pankreas-safra ortak kanalı bağlanırken (PSKB),bir gruba da yalancı-cerrahi (YC) uygulandı. PSKB sıçanlara vagal aferent denervasyon (perivagal kapsaisin; 10mg/ml) veya trunkal vagotomi uygulandı ya da vagusları sağlam bırakıldı. PSKB grupları cerrahi sonrası ikiye ayrılarak 4 gün boyunca intraperitoneal nikotin (1 mg/kg/gün) ya da serum fizyolojik verildi. Dördüncü günde dekapitasyonu takiben, serumda tümör nekroz faktör (TNF)-∝ ve interlökin (IL)-10 ölçümü, akciğer, karaciğer ve pankreas dokularında miyeloperoksidaz aktivitesi (MPO), malondialdehit (MDA), glutatyon (GSH) ölçümleri ve histolojik inceleme yapıldı. TNF-∝ düzeyi PSKB grubunda YC grubuna göre belirgin şekilde daha yüksekken, nikotin tedavisi alanlarda belirgin şekilde daha düşüktü. IL-10 düzeyi ise SF tedavisi almış PSKB grubunda YC grubuna göre daha düşüktü ve nikotin tedavisi ile arttığı gözlendi.YC grubuna göre PSKB grubunun pankreas, karaciğer ve akciğer dokularında mikroskopik hasar, MDA, MPO düzeyleri artarken GSH düzeyleri azaldı. Nikotin tedavisi ile karaciğer ve pankreas dokularındaki hasar, MDA, MPO düzeyleri azaldı ve GSH miktarları korundu. Vagal aferent denervasyon ya da trunkal vagotomi yapılması nikotinin bu koruyucu etkilerini değiştirmedi. Sonuçlar, nikotinin pankreatit hasarına karşı koruyucu etkilerini vagal yoldan bağımsız olarak, doğrudan immün hücreler üzerindeki ∝7nAChR aktivasyonu ile nötrofil infiltrasyonunu ve pro-inflamatuvar sitokinleri inhibe ederek gerçekleştirdiğini ortaya koymaktadır.

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“…In the liver, ConA-bound T cells interact with antigen-presenting cells such as Kupffer cells via MHC-II complex, and consequently, both T cells and Kupffer cells produce inflammatory cytokines and lead to inflammation or cell death in the liver tissue (Tiegs 1997;Krenkel and Tacke 2017). Previous studies have reported that vagus nerve activity is involved in regulating ischemia/reperfusion injury, hepatocyte apoptosis, portal hypertension, inflammatory responses of Kupffer cells, phagocytic activity of macrophages, and oxidative damages in the liver tissues in animal models of liver disease (Zhang et al 2019a;Özdemir-Kumral et al 2017;Bockx et al 2012;Hiramoto et al 2008;Li et al 2014;Nishio et al 2017;Fonseca et al 2019;Metz and Pavlov 2018). It was further shown that T lymphocytes play a role in modulating the inflammatory responses that are controlled by sympathetic and parasympathetic nerve activities (Wong et al 2011;Rosas-Ballina et al 2011), raising the possibility that T lymphocytes activated in ConA-induced hepatitis may be involved in regulating inflammatory responses by VNS.…”

Section: Introductionmentioning

confidence: 99%

Vagal afferent fibers contribute to the anti-inflammatory reactions by vagus nerve stimulation in concanavalin A model of hepatitis in rats

Kim

Namgung

2020

Mol Med

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Background Increasing number of studies provide evidence that the vagus nerve stimulation (VNS) dampens inflammation in peripheral visceral organs. However, the effects of afferent fibers of the vagus nerve (AFVN) on anti-inflammation have not been clearly defined. Here, we investigate whether AFVN are involved in VNS-mediated regulation of hepatic production of proinflammatory cytokines. Methods An animal model of hepatitis was generated by intraperitoneal (i.p.) injection of concanavalin A (ConA) into rats, and electrical stimulation was given to the hepatic branch of the vagus nerve. AFVN activity was regulated by administration of capsaicin (CAP) or AP-5/CNQX and the vagotomy at the hepatic branch of the vagus nerve (hVNX). mRNA and protein expression in target tissues was analyzed by RT-PCR, real-time PCR, western blotting and immunofluorescence staining. Hepatic immune cells were analyzed by flow cytometry. Results TNF-α, IL-1β, and IL-6 mRNAs and proteins that were induced by ConA in the liver macrophages were significantly reduced by the electrical stimulation of the hepatic branch of the vagus nerve (hVNS). Alanine transaminase (ALT) and aspartate transaminase (AST) levels in serum and the number of hepatic CD4+ and CD8+ T cells were increased by ConA injection and downregulated by hVNS. CAP treatment deteriorated transient receptor potential vanilloid 1 (TRPV1)-positive neurons and increased caspase-3 signals in nodose ganglion (NG) neurons. Concomitantly, CAP suppressed choline acetyltransferase (ChAT) expression that was induced by hVNS in DMV neurons of ConA-injected animals. Furthermore, hVNS-mediated downregulation of TNF-α, IL-1β, and IL-6 expression was hampered by CAP treatment and similarly regulated by hVNX and AP-5/CNQX inhibition of vagal feedback loop pathway in the brainstem. hVNS elevated the levels of α7 nicotinic acetylcholine receptors (α7 nAChR) and phospho-STAT3 (Tyr705; pY-STAT3) in the liver, and inhibition of AFVN activity by CAP, AP-5/CNQX and hVNX or the pharmacological blockade of hepatic α7 nAChR decreased STAT3 phosphorylation. Conclusions Our data indicate that the activity of AFVN contributes to hepatic anti-inflammatory responses mediated by hVNS in ConA model of hepatitis in rats.

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Protective Effect of Nicotine on Sepsis-Induced Oxidative Multiorgan Damage: Role of Neutrophils

Cited by 15 publications

References 50 publications

Cholinergic Anti-Inflammatory Pathway and the Liver

Cholinergic Anti-Inflammatory Pathway and the Liver

Investigation of The Role of Vagus in The Ameliorative Effect of Nicotine on Rat Pancreatitis Model

Vagal afferent fibers contribute to the anti-inflammatory reactions by vagus nerve stimulation in concanavalin A model of hepatitis in rats

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